Over 100,000 solid organ transplants are performed annually worldwide, including tens of thousands performed annually in the United States. Despite significant improvements in immunosuppression and post-transplant care, long term graft function is less than optimal. In the United States, adjusted 10 year allograft survival rates for deceased and living donor kidney transplants are only about 40% and 60%, respectively. Early and late stage graft failure, secondary to antibody mediated rejection (AMR) is a significant cause of poor graft survival.
Antibodies to Human Leukocyte Antigens (HLA) are circulating antibodies present in the transplant candidate or recipient's blood which are the result of an earlier sensitization event (blood transfusion, previous transplant, or pregnancy). Donor specific antibodies (DSA) present pre-transplant can cause hyper-acute rejection and immediate graft loss and are assessed by a pre-transplant crossmatch. In more recent years, the concept of monitoring for the post-transplant development of clinically relevant antibodies directed against donor specific HLA class I and class II mismatches has been a significant area of interest within the transplant community. Whether detected pre- or post-transplant, the presence of antibodies directed against antigens expressed on donor organs, when not treated clinically, results in an immune attack on the transplanted organ, and increases risk of graft loss and/or rejection. DSA attacks, among others, the endothelium of the allograft, and can result in subsequent biopsy proven AMR and acute injury requiring augmented immunosuppression. The progression of DSA development and the corresponding clinical events compound to damage the allograft, resulting in chronic changes over time that ultimately compromise graft function and survival.
Antibody mediated rejection can present as an early acute process, resulting from an anamnestic response or de novo antibody production, or as a late and chronic process due to de novo antibody production. In the acute phase, it is often preformed antibodies that cause early rejection, but de novo DSA can also develop in the early post-transplant period, resulting in acute rejection. Patients with preformed DSA are at significantly greater risk of having an acute AMR and have significantly lower graft survival.
Chronic rejection is one of the leading causes of death-censored graft loss. Repeated cycles of alloantibody-mediated injury and repair result in distinct changes in the microvasculature of the allograft. Patients with preformed DSA and those who develop de novo DSA are at an increased risk of having chronic rejection.